Trial Outcomes & Findings for Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza (NCT NCT03684044)
NCT ID: NCT03684044
Last Updated: 2021-01-06
Results Overview
Time to Clinical Improvement (TTCI) is defined as Time to Hospital Discharge OR Time to NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
363 participants
Primary outcome timeframe
Up to Day 35
Results posted on
2021-01-06
Participant Flow
A total of 363 patients received at least one dose of study treatment and were included in the analyses of safety and efficacy.
Participant milestones
| Measure |
Baloxavir Marboxil
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Overall Study
STARTED
|
239
|
124
|
|
Overall Study
COMPLETED
|
217
|
104
|
|
Overall Study
NOT COMPLETED
|
22
|
20
|
Reasons for withdrawal
| Measure |
Baloxavir Marboxil
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
0
|
|
Overall Study
Death
|
4
|
7
|
|
Overall Study
Lost to Follow-up
|
3
|
2
|
|
Overall Study
Patient Not Available
|
0
|
2
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
11
|
9
|
Baseline Characteristics
Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza
Baseline characteristics by cohort
| Measure |
Baloxavir Marboxil
n=239 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=124 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Total
n=363 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.0 Years
STANDARD_DEVIATION 19.8 • n=5 Participants
|
61.6 Years
STANDARD_DEVIATION 20.3 • n=7 Participants
|
59.2 Years
STANDARD_DEVIATION 20.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
117 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
173 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
122 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
190 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
30 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
203 Participants
n=5 Participants
|
106 Participants
n=7 Participants
|
309 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Stated
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
39 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
181 Participants
n=5 Participants
|
95 Participants
n=7 Participants
|
276 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Day 35Population: Participants were reverse transcriptase-polymerase chain reaction (RT-PCR) positive for influenza at any time point
Time to Clinical Improvement (TTCI) is defined as Time to Hospital Discharge OR Time to NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Time to Clinical Improvement
|
97.5 hours
Interval 75.9 to 117.2
|
100.2 hours
Interval 75.9 to 144.4
|
SECONDARY outcome
Timeframe: Day 7Population: All participants who were RT-PCR positive for influenza and were not discontinued or lost to follow up prior to day 7.
The ordinal scale categories are: Category 1) Discharged (or "ready for discharge") Category 2) Non-ICU hospital ward (or "ready for hospital ward") not requiring supplemental oxygen/non-invasive ventilation Category 3) Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen/non-invasive ventilation Category 4) ICU without mechanical (invasive) ventilation (or "ready for ICU admission") Category 5) Mechanical (invasive) ventilation Category 6) Death
Outcome measures
| Measure |
Baloxavir Marboxil
n=199 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=108 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Response Rates of the 6-Point Ordinal Scale at Day 7
Category 1
|
49.2 percentage of participants
|
45.4 percentage of participants
|
|
Response Rates of the 6-Point Ordinal Scale at Day 7
Category 2
|
22.6 percentage of participants
|
24.1 percentage of participants
|
|
Response Rates of the 6-Point Ordinal Scale at Day 7
Category 3
|
20.1 percentage of participants
|
22.2 percentage of participants
|
|
Response Rates of the 6-Point Ordinal Scale at Day 7
Category 4
|
4.0 percentage of participants
|
1.9 percentage of participants
|
|
Response Rates of the 6-Point Ordinal Scale at Day 7
Category 5
|
3.5 percentage of participants
|
4.6 percentage of participants
|
|
Response Rates of the 6-Point Ordinal Scale at Day 7
Category 6
|
0.5 percentage of participants
|
1.9 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Participants were RT-PCR positive for influenza at any time point
Time to Clinical Response is based on temperature ranges, oxygen saturation, respiratory status, heart rate, and hospitalization status.
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Time to Clinical Response
|
138.3 hours
Interval 120.0 to 161.1
|
145.1 hours
Interval 128.0 to 187.2
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Participants were RT-PCR positive for influenza at any time point
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Percentage of Participants on Mechanical Ventilation
|
5.3 percentage of participants
|
6.1 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Participants were RT-PCR positive for influenza at any time point
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Duration of Mechanical Ventilation
|
150.25 hours
Interval 18.0 to 465.0
|
91.00 hours
Interval 24.0 to 407.0
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Participants were RT-PCR positive for influenza at any time point
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Percentage of Participants Requiring ICU Stay
|
4.3 percentage of participants
|
3.5 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Participants were RT-PCR positive for influenza at any time point
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Duration of ICU Stay
|
138.55 hours
Interval 23.7 to 362.0
|
71.78 hours
Interval 18.7 to 139.4
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Participants were RT-PCR positive for influenza at any time point
Time to clinical failure, defined as the time to death, mechanical ventilation, or ICU admission, corresponding to ordinal scale categories 6, 5, and 4, respectively, from baseline
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Time to Clinical Failure
|
NA hours
Very few patients experienced a clinical failure event and the median time to clinical failure could not be estimated .
|
NA hours
Very few patients experienced a clinical failure event and the median time to clinical failure could not be estimated .
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Participants were RT-PCR positive for influenza at any time point
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Time to Hospital Discharge
|
166.7 hours
Interval 144.7 to 190.7
|
167.3 hours
Interval 146.4 to 211.1
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Participants were RT-PCR positive for influenza at any time point
Influenza-related complications included pneumonia, myositis or rhabdomyolysis, encephalitis or encephalopathy, myocarditis and/or pericarditis, otitis media, sinusitis, exacerbation of COPD/asthma, sepsis, acute lung injury or acute respiratory distress syndrome.
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Percentage of Participants With Post-Treatment Influenza-Related Complications
|
10.6 percentage of participants
|
14.0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Day 7Population: Participants were RT-PCR positive for influenza at any time point
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Mortality Rate at Day 7
|
0.5 percentage of participants
Interval 0.01 to 2.65
|
2.6 percentage of participants
Interval 0.55 to 7.5
|
SECONDARY outcome
Timeframe: Up to Day 28Population: Participants were RT-PCR positive for influenza at any time point
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Mortality Rate at Day 28
|
1.9 percentage of participants
Interval 0.53 to 4.85
|
5.3 percentage of participants
Interval 1.96 to 11.1
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Participants were RT-PCR positive for influenza at any time point
A score of 0 (Range 0 - 3) indicates normal health conditions.
Outcome measures
| Measure |
Baloxavir Marboxil
n=208 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=114 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Time to NEWS2 of ≤ 2 Maintained for 24 Hours
|
106.3 hours
Interval 88.3 to 138.3
|
127.2 hours
Interval 77.4 to 156.3
|
SECONDARY outcome
Timeframe: Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10Population: Participants were RT-PCR positive for influenza at any time point and with a positive virus titer on Day 1
Time to cessation of viral shedding by virus titer is defined as the time, in hours, between the initiation of study treatment and first time when the influenza virus titer is below the limit of detection (0.75 log10 TCID50/mL)
Outcome measures
| Measure |
Baloxavir Marboxil
n=159 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=78 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Time to Cessation of Viral Shedding by Virus Titer
|
23.9 hours
Interval 23.2 to 24.5
|
63.7 hours
Interval 46.4 to 68.1
|
SECONDARY outcome
Timeframe: Days 2, 3, 4, 5, 7, and 10Population: Participants were RT-PCR positive for influenza at any time point and with a positive virus titer on Day 1
Influenza virus titer is the quantity of influenza virus in a given volume within the samples obtained from nasal swabs. If influenza virus titer was less than the lower limit of quantification, the virus titer was imputed as 0.749 (log10TCID50/mL). A lower value indicates lower viral titer.
Outcome measures
| Measure |
Baloxavir Marboxil
n=159 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=78 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Change From Baseline in Influenza Virus Titer at Each Timepoint
Day 2
|
-2.36 log10 TCID50/ml
|
-1.00 log10 TCID50/ml
|
|
Change From Baseline in Influenza Virus Titer at Each Timepoint
Day 3
|
-2.70 log10 TCID50/ml
|
-1.93 log10 TCID50/ml
|
|
Change From Baseline in Influenza Virus Titer at Each Timepoint
Day 4
|
-2.88 log10 TCID50/ml
|
-2.50 log10 TCID50/ml
|
|
Change From Baseline in Influenza Virus Titer at Each Timepoint
Day 5
|
-3.01 log10 TCID50/ml
|
-2.81 log10 TCID50/ml
|
|
Change From Baseline in Influenza Virus Titer at Each Timepoint
Day 7
|
-3.00 log10 TCID50/ml
|
-2.95 log10 TCID50/ml
|
|
Change From Baseline in Influenza Virus Titer at Each Timepoint
Day 10
|
-3.02 log10 TCID50/ml
|
-3.06 log10 TCID50/ml
|
SECONDARY outcome
Timeframe: Days 2, 3, 4, 5, 7, and 10Population: Participants were RT-PCR positive for influenza at any time point and with a positive virus titer on Day 1.
Influenza virus titer is the quantity of influenza virus in a given volume within the samples obtained from nasal swabs. If influenza virus titer was less than the lower limit of quantification, the virus titer was imputed as 0.749 (log10 TCID50/mL). A lower value indicates lower viral titer.
Outcome measures
| Measure |
Baloxavir Marboxil
n=159 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=78 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint
Day 2
|
37.7 percentage of participants
|
80.3 percentage of participants
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint
Day 3
|
18.6 percentage of participants
|
53.4 percentage of participants
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint
Day 4
|
7.9 percentage of participants
|
26.7 percentage of participants
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint
Day 5
|
1.3 percentage of participants
|
20.8 percentage of participants
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint
Day 7
|
2.7 percentage of participants
|
5.8 percentage of participants
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint
Day 10
|
1.4 percentage of participants
|
1.4 percentage of participants
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 7, and 10Population: Participants with a positive virus titer on Day 1
Outcome measures
| Measure |
Baloxavir Marboxil
n=159 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=77 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Area Under the Curve in Virus Titer
|
291.68 log10 TCID50/mL*hours
Standard Deviation 176.68
|
332.04 log10 TCID50/mL*hours
Standard Deviation 183.63
|
SECONDARY outcome
Timeframe: Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10Population: Participants were RT-PCR positive for influenza on Day 1
Time to cessation of viral shedding by RT-PCR, in hours, is defined as the time between the initiation of study treatment and first time when the virus RNA by RT-PCR is below the limit of detection (2.05 for flu A and 2.83 for flu B log10 virus particles/mL)
Outcome measures
| Measure |
Baloxavir Marboxil
n=205 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=111 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Time to Cessation of Viral Shedding by RT-PCR
|
216.3 hours
Interval 211.3 to 239.8
|
261.1 hours
Interval 236.4 to
Due to low number of events the upper limit of the 95% confidence interval (CI) was not evaluable
|
SECONDARY outcome
Timeframe: Days 2, 3, 4, 5, 7, and 10Population: Participants were RT-PCR positive for influenza on Day 1
If the amount of virus RNA was less than the lower limit of quantification, the amount of virus RNA was imputed as 2.18 for flu A and 2.93 for flu B (log10 virus particles/mL)
Outcome measures
| Measure |
Baloxavir Marboxil
n=205 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=111 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint
Day 2
|
-0.98 log10 virus particles/mL
|
-0.66 log10 virus particles/mL
|
|
Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint
Day 3
|
-1.54 log10 virus particles/mL
|
-1.19 log10 virus particles/mL
|
|
Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint
Day 4
|
-2.35 log10 virus particles/mL
|
-1.84 log10 virus particles/mL
|
|
Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint
Day 5
|
-2.91 log10 virus particles/mL
|
-2.39 log10 virus particles/mL
|
|
Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint
Day 7
|
-3.15 log10 virus particles/mL
|
-2.96 log10 virus particles/mL
|
|
Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint
Day 10
|
-3.69 log10 virus particles/mL
|
-3.21 log10 virus particles/mL
|
SECONDARY outcome
Timeframe: Days 2, 3, 4, 5, 7, and 10Population: Participants were RT-PCR positive for influenza on Day 1
If the amount of virus RNA was less than the lower limit of quantification, the amount of virus RNA was imputed as 2.18 for flu A and 2.93 for flu B (log10 virus particles/mL)
Outcome measures
| Measure |
Baloxavir Marboxil
n=205 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=111 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Percentage of Participants Positive by RT-PCR at Each Timepoint
Day 2
|
95.6 percentage of participants
|
96.3 percentage of participants
|
|
Percentage of Participants Positive by RT-PCR at Each Timepoint
Day 3
|
90.0 percentage of participants
|
93.3 percentage of participants
|
|
Percentage of Participants Positive by RT-PCR at Each Timepoint
Day 4
|
88.1 percentage of participants
|
87.9 percentage of participants
|
|
Percentage of Participants Positive by RT-PCR at Each Timepoint
Day 5
|
79.9 percentage of participants
|
85.4 percentage of participants
|
|
Percentage of Participants Positive by RT-PCR at Each Timepoint
Day 7
|
69.6 percentage of participants
|
68.0 percentage of participants
|
|
Percentage of Participants Positive by RT-PCR at Each Timepoint
Day 10
|
46.7 percentage of participants
|
50.5 percentage of participants
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 7, and 10Population: Participants were RT-PCR positive for influenza on Day 1.
Outcome measures
| Measure |
Baloxavir Marboxil
n=197 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=106 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Area Under the Curve in the Amount of Virus RNA (RT-PCR)
|
676.40 log10 virus particles/mL*hours
Standard Deviation 371.72
|
740.15 log10 virus particles/mL*hours
Standard Deviation 484.07
|
SECONDARY outcome
Timeframe: Up to Day 35An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A serious adverse event (SAE) is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Outcome measures
| Measure |
Baloxavir Marboxil
n=239 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=124 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
45.2 percentage of participants
|
50.0 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
12.1 percentage of participants
|
15.3 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Day 35Discontinuation from study treatment.
Outcome measures
| Measure |
Baloxavir Marboxil
n=239 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=124 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Percentage of Participants With AEs and SAEs Leading to Discontinuation From Treatment
AEs
|
1.3 percentage of participants
|
3.2 percentage of participants
|
|
Percentage of Participants With AEs and SAEs Leading to Discontinuation From Treatment
SAEs
|
0.8 percentage of participants
|
1.6 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Day 35ALT = alanine aminotransferase AST = aspartate transaminase
Outcome measures
| Measure |
Baloxavir Marboxil
n=239 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=124 Participants
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Percentage of Participants With Any Post-Treatment ALT and AST Above Baseline and >3 × ULN, >5 × ULN, >10 × ULN
AST(U/L) or ALT (U/L) >3 x ULN
|
4.6 percentage of participants
|
8.9 percentage of participants
|
|
Percentage of Participants With Any Post-Treatment ALT and AST Above Baseline and >3 × ULN, >5 × ULN, >10 × ULN
AST(U/L) or ALT (U/L) >5 x ULN
|
0.8 percentage of participants
|
3.2 percentage of participants
|
|
Percentage of Participants With Any Post-Treatment ALT and AST Above Baseline and >3 × ULN, >5 × ULN, >10 × ULN
AST(U/L) or ALT (U/L) >10 x ULN
|
0 percentage of participants
|
1.6 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1, 2, 4, 5, 7 and 8Population: Participants who provided informed consent to intensive PK sampling in the Baloxavir Marboxil arm.
Outcome measures
| Measure |
Baloxavir Marboxil
n=8 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 1 - 30 minutes postdose
|
37.82 ng/mL
Standard Deviation 23.61
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 1 - 2 hours postdose
|
75.06 ng/mL
Standard Deviation 52.16
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 1 - 4 hours postdose
|
95.85 ng/mL
Standard Deviation 58.36
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 1 - 10 hours postdose
|
64.47 ng/mL
Standard Deviation 39.47
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 2 - 24 hours postdose
|
53.36 ng/mL
Standard Deviation 37.42
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 4 - Predose
|
24.26 ng/mL
Standard Deviation 15.87
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 4 - 30 minutes postdose
|
49.16 ng/mL
Standard Deviation 52.07
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 4 - 2 hours postdose
|
109.66 ng/mL
Standard Deviation 95.22
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 4 - 4 hours postdose
|
117.69 ng/mL
Standard Deviation 60.54
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 4 - 10 hours postdose
|
94.08 ng/mL
Standard Deviation 49.71
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 5 - 24 hours postdose
|
77.98 ng/mL
Standard Deviation 42.89
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 7 - predose
|
23.31 ng/mL
Standard Deviation 25.87
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Day 8 - 24 hours postdose
|
105.00 ng/mL
Standard Deviation NA
Not applicable as only 1 participant was analyzed
|
—
|
|
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Visit 8
|
28.37 ng/mL
Standard Deviation 61.61
|
—
|
SECONDARY outcome
Timeframe: 0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8Population: Participants who provided informed consent to intensive pharmacokinetic (PK) sampling in the Baloxavir Marboxil arm.
Outcome measures
| Measure |
Baloxavir Marboxil
n=8 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Area Under the Concentration to Time Curve From Time 0 to 72 Hours (AUC0-72) of Baloxavir
Day 1
|
2820 Hours(h)*nanogram(ng)/milliliter (mL)
Geometric Coefficient of Variation 70.5
|
—
|
|
Area Under the Concentration to Time Curve From Time 0 to 72 Hours (AUC0-72) of Baloxavir
Day 4
|
3170 Hours(h)*nanogram(ng)/milliliter (mL)
Geometric Coefficient of Variation 53.5
|
—
|
SECONDARY outcome
Timeframe: 0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8Population: Participants who provided informed consent to intensive PK sampling in the Baloxavir Marboxil arm.
Outcome measures
| Measure |
Baloxavir Marboxil
n=8 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Baloxavir
Day 1
|
86.3 ng/mL
Geometric Coefficient of Variation 64.6
|
—
|
|
Maximum Plasma Concentration (Cmax) of Baloxavir
Day 4
|
123 ng/mL
Geometric Coefficient of Variation 51.7
|
—
|
SECONDARY outcome
Timeframe: 0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8Population: Participants who provided informed consent to intensive PK sampling and had a sufficient number of samples available for analysis
Outcome measures
| Measure |
Baloxavir Marboxil
n=8 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Apparent Half-Life (T1/2) of Baloxavir
Day 1
|
18.9 Hours (h)
Geometric Coefficient of Variation NA
Not estimable as only 1 participant was eligible for the assessment of this measure
|
—
|
|
Apparent Half-Life (T1/2) of Baloxavir
Day 4
|
23.4 Hours (h)
Geometric Coefficient of Variation 12.8
|
—
|
SECONDARY outcome
Timeframe: 0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8Population: Participants who provided informed consent to intensive PK sampling in the Baloxavir Marboxil arm
Outcome measures
| Measure |
Baloxavir Marboxil
n=8 Participants
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Concentration at 24 Hours (C24) of Baloxavir
Day 1
|
43.9 ng/mL
Geometric Coefficient of Variation 74.4
|
—
|
|
Concentration at 24 Hours (C24) of Baloxavir
Day 4
|
67.1 ng/mL
Geometric Coefficient of Variation 66.8
|
—
|
|
Concentration at 24 Hours (C24) of Baloxavir
Day 7
|
105 ng/mL
Geometric Coefficient of Variation NA
Not applicable as only 1 participant was analyzed
|
—
|
Adverse Events
Baloxavir Marboxil
Serious events: 29 serious events
Other events: 44 other events
Deaths: 4 deaths
Placebo
Serious events: 19 serious events
Other events: 27 other events
Deaths: 7 deaths
Serious adverse events
| Measure |
Baloxavir Marboxil
n=239 participants at risk
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=124 participants at risk
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Cardiac disorders
Acute myocardial infarction
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Cardiac disorders
Atrial fibrillation
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Cardiac disorders
Bradycardia
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Cardiac disorders
Cardiac failure
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Cardiac disorders
Congestive cardiomyopathy
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Cardiac disorders
Myocardial ischaemia
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.84%
2/239 • Number of events 2 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Immune system disorders
Graft versus host disease
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Infections and infestations
Asymptomatic bacteriuria
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Infections and infestations
Bronchitis
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Infections and infestations
Cellulitis
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Infections and infestations
Clostridium difficile colitis
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Infections and infestations
Device related infection
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Infections and infestations
Endocarditis
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Infections and infestations
Lower respiratory tract infection viral
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Infections and infestations
Pneumonia
|
2.9%
7/239 • Number of events 7 • Randomization up to Day 35
|
4.0%
5/124 • Number of events 5 • Randomization up to Day 35
|
|
Infections and infestations
Pneumonia bacterial
|
0.84%
2/239 • Number of events 2 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Infections and infestations
Pneumonia viral
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Infections and infestations
Sepsis
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Infections and infestations
Septic shock
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Infections and infestations
Superinfection viral
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Nervous system disorders
Cerebral artery embolism
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Product Issues
Device malfunction
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.84%
2/239 • Number of events 2 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.42%
1/239 • Number of events 2 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.3%
3/239 • Number of events 4 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/239 • Randomization up to Day 35
|
1.6%
2/124 • Number of events 2 • Randomization up to Day 35
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Vascular disorders
Aortic aneurysm rupture
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Vascular disorders
Hypotension
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/239 • Randomization up to Day 35
|
0.81%
1/124 • Number of events 1 • Randomization up to Day 35
|
|
Vascular disorders
Peripheral ischaemia
|
0.42%
1/239 • Number of events 1 • Randomization up to Day 35
|
0.00%
0/124 • Randomization up to Day 35
|
Other adverse events
| Measure |
Baloxavir Marboxil
n=239 participants at risk
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
Placebo
n=124 participants at risk
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
4.2%
10/239 • Number of events 10 • Randomization up to Day 35
|
4.8%
6/124 • Number of events 6 • Randomization up to Day 35
|
|
Gastrointestinal disorders
Diarrhoea
|
3.3%
8/239 • Number of events 8 • Randomization up to Day 35
|
4.8%
6/124 • Number of events 7 • Randomization up to Day 35
|
|
Gastrointestinal disorders
Nausea
|
2.9%
7/239 • Number of events 9 • Randomization up to Day 35
|
3.2%
4/124 • Number of events 4 • Randomization up to Day 35
|
|
Infections and infestations
Pneumonia
|
2.1%
5/239 • Number of events 6 • Randomization up to Day 35
|
3.2%
4/124 • Number of events 4 • Randomization up to Day 35
|
|
Investigations
Hepatic enzyme increased
|
2.5%
6/239 • Number of events 7 • Randomization up to Day 35
|
4.0%
5/124 • Number of events 5 • Randomization up to Day 35
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
3.8%
9/239 • Number of events 9 • Randomization up to Day 35
|
4.0%
5/124 • Number of events 5 • Randomization up to Day 35
|
|
Nervous system disorders
Headache
|
3.8%
9/239 • Number of events 11 • Randomization up to Day 35
|
1.6%
2/124 • Number of events 2 • Randomization up to Day 35
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER